An R&D Blueprint for action to prevent epidemics · An R&D Blueprint for action to prevent...

An R&D Blueprint for action to prevent epidemics

Report to the Scientific Advisory Group

8-9 February 2017

8-9 February 2017 | R&D Blueprint SAG meeting

Why an R&D Blueprint?

The Ebola epidemic has demonstrated that it is possible to accelerate R&D during emergencies and that it is feasible to safely and effectively implement research interventions in an affected country.

It also highlighted the imperative to advance R&D preparedness and effective collaboration frameworks in advance of any new epidemic.


Operational objective of the Blueprint

The R&D Blueprint seeks to create an enabling

environment through which all actors, through increased

funding, data sharing and partnerships, can drive change

in the public health landscape to provide an elevated level

of global impact.

Declaration of PHEIC

emergency

… Day 0…I…I…I…I…I…I…I…I…I…I…I…I… Day available

…

Availability of

effective diagnostics, therapeutics &

vaccines


Ebola vaccine efficacy trial


What is the Blueprint?

• a global strategy and preparedness plan

• a convening

mechanism and an

instrument to articulate technical guidance


The Blueprint approaches are aligned with:

the lessons learned during the 2014–2016 Ebola epidemic and

the recommendations of the various reviews on the Ebola epidemic conducted to date


4 principles

1 An inclusive

process with

a clear

mandate

and defined

milestones

2 Building on

the efforts of

others in the

community

3 A collaborative

effort with the

Member States

in the affected

countries at the

core of it

4 Driven by

scientific

knowledge


Approaches to improve preparedness under the R&D Blueprint

1.Building an effective governance & coordination

framework

2.Outlining transparent and aligned funding process

3.Encouraging effective communication

1.Assessing epidemic threat & defining priority

pathogens

2.Developing R&D roadmaps to accelerate

evaluation of Dx, therapeutics & vaccines

3.Outlining regulatory & ethical pathways

1.Supporting expansion of capacity to implement

adequate study designs

2.Developing guidance & tools

3.Anticipating evidence needs for regulatory review

and policy development


Monitoring the impact

IMPACT LONG-TERM OUTCOMES MEDIUM-TERM

OUTCOMES OUTPUTS INPUTS

For unknown

pathogens, R&D

projects

implemented by

various

stakeholders

towards required

research are well

coordinated to

ensure maximum

efficacy

For known

pathogens,

products are ready

for phase 2/3

clinical testing and

knowledge of the

diseases is at an

advanced stage

R&D responses to

Public Health

Emergencies of

International

Concern caused by

prioritized or

previously unknown

pathogens are faster,

more effective, more

efficient and

conducted with

greater consideration

for affected people.

Lives saved

Epidemics averted

Infections prevented

or cured

Economic benefits

of improved health

realized

Assumes right mix of programme management and

technical staff available to

WHO

Assumes effective

communication and

coordination across WHO regional and country offices

Assumes WHO works effectively and collaboratively with other actors

Assumes financial resources are available for all

Blueprint activities and responses that are needed

Assumes that effective R&D

is an essential element in responding to public health

emergencies

Assumes that public health emergencies due to

prioritized pathogens will be

a major cause of illness, death and negative

economic consequences in

the absence of effective responses

Coordination

improved and an

enabling

environment

fostered

Scientific expertise,

leadership and

management

Research and

development

processes

accelerated

New norms and

standards

developed

adapted to the

epidemic context Crosscutting activities

to coordinate,

communicate about,

monitor and evaluate

the Blueprint

Streamlining

operational R&D

response during

outbreaks

Response plan to

outbreaks

developed

Activities conducted

within three

approaches

R&D during a

Public Health

Emergency of

International

Concern is more

coordinated


Operationalizing the Blueprint

Steering Group 2 WHO Clusters HIS, FWC

and WHE programme Management team

Scientific Advisory Group

HIS Priority pathogens

Regulatory & ethical pathways TPPs/data sharing/MTAs Monitoring & Evaluation

Financial Admin Blueprint Communication

FWC Global coordination

Roadmaps Clinical trials capacity

WHE R&D plans during

outbreaks


Main recent achievements

• Steps to create the Global Coordination Framework

• Revised list of prioritized pathogens • MERS-CoV roadmap • TPPs for Zika, MERS-CoV, Ebola • EUAL procedure • Zika R&D response • Identification of potential platform technologies

• ICMJE guidelines for sharing results • Steps to inform discussions on trial designs • Developing MTA capacity building tool


An expanding network of partners and collaborators • Observer on the GloPID-R assembly • Collaboration with CEPI

• Invaluable support and inputs from numerous partners

including: • Wellcome Trust • BARDA, NIH, CDC, Chatham House, Inst Pasteur • MSF, UNICEF • BMGF • FDA, EMA • Numerous academic institutions: U of Florida, LSHTM, U of

Laval, U of Texas, EmLab …..


WHO Principles for engaging with CEPI

An MoU to frame the collaboration

• Any vaccine coming out of CEPI's efforts will be available to

and affordable for those in need;

• The price of the vaccine coming out of CEPI's efforts will be delinked from the costs of R&D;

• Collaboration will be based on an open basis;

• IP will be managed in a manner which maximizes access;

• CEPI will be transparent and open to all actors, large and small, from the North and the South. Funding will be based on merit;

• As CEPI will be based on public and philanthropic funding, it will operate on a "shared benefit" basis.

Due diligence under FENSA was conducted and collaboration with CEPI was authorized.

The R&D Blueprint represents WHO’s new start

for a better R&D preparedness.

The current lack of R&D preparedness

is a problem that can be solved.

Let’s solve it together.

The WHO Research & Development Blueprint

Scientific Advisory Group meeting

8-9 February 2017

Improving coordination and fostering an enabling environment

Report to the R&D Blueprint Scientific Advisory Group Geneva, 8-9 February 2017

2015 2016 2017

2015 2016 2017

2015 2016 2017

Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 BEYOND

Start mapping of key

stakeholders to have an

overview of existing

initiatives & stakeholders

Consultation with

stakeholders &

identification of funding

options

Average

funding needs

estimated

Report of financial options finalised

and published

Scientific interactions: Zika, Mers-Cov, … …

ZIKA

open

Blueprint SAG and other consultations



Develop a template framework to streamline global

stakeholder collaboration

Scoping meeting

Global Coordination

Mechanism

Encouraging

effective

communicatio

n

Outlining

innovative

transparent and

aligned funding

processes

Building an

effective

governance &

coordination

framework

Improving coordination & fostering an enabling environment A

Formalise and get operational a mechanism for improved

and coordinated R&D preparedness and response capacity

Page 1 of 3

Establishing a Global Coordination Mechanism for Research and

Development to Prevent and Respond to Epidemics: Scoping Meeting

The global health community increasingly recognizes the importance of proactive,

collaborative and coordinated research and development (R&D) efforts to save people’s

lives and avert public health crisis. These efforts - in advance of and during epidemics -

must overcome existing market failures. Mandated by its Member States, the WHO

Blueprint for Research Preparedness aims to reduce the time lag between an epidemic

and the availability of medical countermeasures for use in the field. Under the Blueprint

Plan of Action, WHO has prioritized nine pathogens which could trigger epidemics in

the near future and for which no licensed medical countermeasures exist. Given the

complexity of R&D processes and the timescale usually associated with the development

of medical countermeasures, a mechanism to coordinate the global R&D agenda is

needed in order to ensure a rapid and effective R&D preparedness and response.

This document is a short summary of discussions that took place on 10 November 2016,

convened by Chatham House. The aim of the meeting was to stimulate a high-quality

dialogue among experts from a broad range of public health and R&D environments to

define the need for, and principles of, a Global Coordination Mechanism (GCM) for

R&D to prevent and respond to epidemics.

General Discussion

The Nature of Global R&D Coordination

The nature of the global R&D coordination needed was extensively discussed. It

was agreed that the primary role of a coordinating mechanism would be to

address the global R&D agenda in a collaborative manner in order to ensure that

identified R&D gaps are being filled effectively. To be successful, the coordination

mechanism would need a consensual governance framework to which key

stakeholders have adhered. In short, the mechanism would identify what should

be done and ensure that progress is being made, rather than attempting to

operationalize all activities. As a result, a high-level continuum between

coordination and governance would be needed in order bridge the recognised

misalignments in R&D preparedness and response.

It was acknowledged that a global fund for epidemic R&D preparedness would be

ideal but the lack of donors’ appetite for such a fund was acknowledged.

Centre on Global Health Security

Meeting Summary

November 2016 A first scoping meeting co-hosted by Chatham House, the Wellcome Trust and WHO brought together key stakeholders in global R&D


The Nature of Global R&D Coordination The primary role of a coordinating mechanism would be to address the global R&D agenda in a collaborative manner in order to ensure that identified R&D gaps are being filled effectively. To be successful, the coordination mechanism would need a consensual governance framework to which key stakeholders have adhered. A high-level continuum between coordination and governance would be needed in order bridge the recognised misalignments in R&D preparedness and response

A Global Coordination Mechanism


The Scope of the Coordination Mechanism The WHO Blueprint Plan of Action focus primarily on R&D activities associated with the development and availability of medical countermeasures. Coordination during emergencies can only be successful if it builds on established coordination. Therefore, coordination should take place throughout preparedness, in getting relevant actors together, as well as during public health emergency operations.



Activities 2017 All agreed that a Global Coordination Mechanism (GCM) led by WHO was needed. March 28, 2017 - A further meeting will be convened in to review the proposed scope and terms of reference of the GCM and to agree on the establishment of the GCM. Zika as a test case of the GCM. 2nd Quarter 2017 - Complete visualization tools on existing networks and initiatives relevant to this work.


2015 2016 2017

2015 2016 2017

2015 2016 2017


Start mapping of key

stakeholders to have an

overview of existing

initiatives & stakeholders

Consultation with

stakeholders &

identification of funding

options

Average

funding needs

estimated

Report of financial options finalised

and published

Scientific interactions: Zika, Mers-Cov, … …

ZIKA

open

Blueprint SAG and other consultations



Develop a template framework to streamline global

stakeholder collaboration

Scoping meeting

Global Coordination

Mechanism

Encouraging

effective

communicatio

n

Outlining

innovative

transparent and

aligned funding

processes

Building an

effective

governance &

coordination

framework

Improving coordination & fostering an enabling environment A

Formalise and get operational a mechanism for improved

and coordinated R&D preparedness and response capacity

What are the anticipated benefits? Global response efforts are faster, more consistent, transparent and better coordinated, with less waste and redundancy. Ownership and buy-in from key stakeholders and communities are increased. The enabling environment will allow effective, transparent and equitable collaboration between the contributing stakeholders to produce the desired result: an effective response to public health emergencies that is quick and efficient.

Assessing epidemic threat and defining priority pathogens

2015 2016 2017

2015 2016 2017

2015 2016 2017


1st priority list of

pathogens developed

Updated list of priority pathogens generated

Prototype roadmap for

MERS-Cov developed

Consultation process to

identify & evaluate

technology platforms Methodology to

develop roadmaps

Guidelines on regulatory evaluation outlined

Production of international

reference preparations

Regulatory pathways outlined and finalised



Review of

prioritisation

methodology

Generic pathogen

scenarios outlined Prioritisation

methodology

set up

Outlining

appropriate

regulatory &

ethical

pathwaysys

Developing R&D

roadmaps to

accelerate

evaluation of Dxs,

therapeutics &

vaccines

Develop roadmaps for priority pathogens & generic TPPs

Assessing epidemic

threat & defining

priority pathogens

Insurance options for

clinical trials in the context

of epidemics

Ethical guidelines in the

context of epidemics


Overview of the prioritization process

All possible

pathogens &

pathogens

List of

contenders for

prioritization

Prioritized list of

pathogens &

pathogens

Landscape

analysis

Delphi process

Ranking the

pathogens

Assessing

confidence in

the prioritized

list

Promoting the prioritized list

Triaging list of

pathogens to be considered

Ranking the

long list of

pathogens & pathogens

Post-

prioritization activities

Routine reviews Emergency

Decision

instrument

Emergency

prioritization exercise

New

pathogen


Timeline

May 2015 – WHO international consultation on Blueprint

December 2015 – WHO informal consultation on priority pathogens

Early 2016 – Blueprint team develops methodology outline

May 2016 – SAG reviews methodology outline

Summer / Autumn 2016 – Detailed methodology developed

December 2016 – Informal consultation reviews & validates methodology

January 2017 – Annual review of list of priority pathogens

Activities undertaken to-date


Prioritization criteria Factors used to prioritize pathogens

Criteria Weights

Human transmissibility 32%

Medical countermeasures 21.90%

Severity 14.65%

Human/animal interface 9.42%

Other contributing factors 9.42%

Public health context of the affected area 6.13%

Potential social impacts 4.18%

Evolutionary potential 2.28%


List of priority pathogens 2017

• Lassa Fever and other severe Arenaviral haemorrhagic fevers

• Crimean Congo Haemorrhagic Fever

• Filoviral pathogens (including Ebola and Marburg)

• MERS-CoV

• Other high-path coronaviral pathogens (such as SARS)

• Nipah and related henipaviral pathogens

• Rift Valley Fever

• Severe fever with thrombocytopenia syndrome

• Zika

And any pathogen identified by the decision instrument

Chikungunya Virus continues to warrant further research and development.

(The order of pathogens on this list does not denote any ranking of priority)


Other pathogens were considered & a wide range of additional relevant R&D initiatives encouraged

• Cross-cutting R&D to address multiple pathogens

• One-Health approach

• Anti-microbial resistance

Other areas of substantial output

1. Emerging flaviviruses (such as Kyasanur Forest pathogen or Usutu); 2. Emerging Bunyaviruses (such as Oropouche); 3. Emerging Alphaviruses (such as Chikungunya & Mayaro virus); 4. Rickettsia; 5. Plague; 6. Hantaviral pathogens; 7. Chandipura virus pathogen.

What are the anticipated benefits? Factors that are important to identify priority pathogens are known. A decision tree for determining when a novel pathogen would trigger an interim prioritization assessment is available.

R&D Blueprint Roadmaps

2015 2016 2017

2015 2016 2017

2015 2016 2017



pathogens developed



MERS-Cov developed


identify & evaluate


develop roadmaps







Review of

prioritisation

methodology

Generic pathogen


methodology

set up

Outlining

appropriate

regulatory &

ethical

pathwaysys

Developing R&D

roadmaps to

accelerate

evaluation of Dxs,

therapeutics &

vaccines


Assessing epidemic

threat & defining

priority pathogens



of epidemics




R&D Blueprint Roadmaps

WHO R&D Blueprint

priority pathogens any necessary actions for such priority pathogens

coordinated through pathogen-specific initiatives

design of R&D roadmaps to accelerate evaluation of medical countermeasures

diagnostics, therapeutics and vaccines

R&D Blueprint roadmaps Vision, strategic goals and priorities towards accelerated R&D

from basic research through to late-stage development, licensure and early use of products

to prevent and control pathogens due to priority pathogens


Context WHO to lead on a future Global Coordination Mechanism (GCM) for R&D preparedness and response - Round Table, Chatham House 10

November 2016

In terms of R&D Roadmaps, WHO will

o Lead, coordinate and ensure continuous oversight

o Establish and refine the generic methodology

o For each roadmap

1. Baseline situation analysis (background paper)

2. Identify and Engage Partners

3. WHO target product profiles

o Develop and maintain a dashboard

o Ensure publication of roadmaps as joint products


Context (cont’d)

As commissioned, each roadmap taskforce will be responsible for:


A generic methodology Developing and implementing R&D Roadmaps for priority pathogens with epidemic potential

R&D Blueprint roadmaps will form a strategic framework that underpins

strategic goals and research priorities of the global R&D community

developed on the basis of

a generic methodology purpose: to provide a standardized

procedure that structures and harmonizes the development and implementation of

R&D roadmaps

First draft circulated for internal review on 1 February 2017

Presentation to SAG

Advanced draft to be circulated to external selected experts for comments

Working draft by mid-March 2017


A generic methodology

Methodology Synopsis High level overview of principles and concepts, intended for peer-review publication Methodology Core Document Outline of the structure, design and implementation Appendices Detailed instructions/steps for each of the roadmap

elements


Activities 2017 Ebola -

Marburg CCHF Zika Lassa

Consultant,

collaborating

centre

(BSA)

Taskforce

(roadmap)

Roadmap

expected End Q2 End Q3 End Q4

End Q3

TPP Diagnostics

Ebola Vaccine

Multivalent-

Filovirus-vaccine

Diagnostics

Vaccines

ongoing identified to be done


Discussion

What are the anticipated benefits? The R&D roadmaps identify R&D gaps and help prioritize where investments should be channelled to initiate R&D initiatives; this will hopefully translate into interest from funders.

Target Product Profiles

External Working Group

Public Consultation

PDVAC, Finalise, Update

TPP Process Baseline analysis


MERS-CoV Vaccine TPPs

• Draft TPPs for 2 human vaccines and 1 camel vaccine

open for public consultation

• Collaboration with OIE mobilizing animal vaccine

stakeholders

Product Phase Country

DNA vaccine Phase 1 since 2016 USA

SAB Polyclonal Phase 1 since 2016 USA

MVA vaccine Phase 1 Q1 2017 Germany

? Vaccine Phase 1 2017 South Korea

Chimp Ad vaccine Phase 1 2017 UK

Chimp Ad vaccine In camel testing Chad


Development timeline for vaccine TPPs Circulation of draft TPP to Expert Working group for comments

Public consultation of draft TPPs

Final TPP published at WHO website

Monovalent Ebola – reactive and preventive use

2015

Multivalent filovirus vaccine TPP – preventive use

Oct 2016 Nov 2016

Revised Zika virus vaccine TPP (first version, published July 2016)

Dec 2016 Feb 2017

MERS Co-V vaccine TPPs (3)

Feb 2017 March 2017

Nipah Virus vaccine TPP

Q1 Q1 Q2

Lassa Fever virus vaccine TPP

Q1 Q2 Q2


Development timeline for diagnostic TPPs

Circulation of draft TPP to Expert Working group for comments

Public consultation of draft TPPs

Final TPP published at WHO website

Zika virus diagnostics

March 2016 April 2016

April 2016

Revised Ebola virus diagnostics (first version, published Oct 2014)

July 2017 August 2017 September 2017

MERS CoV Q3 Q4

Also planned for 2017: MERS-CoV TPP including multivalent respiratory test for syndromic diagnosis of SARI (severe acute respiratory illness), approach to other syndromic diagnostics will be explored

Regulatory Pathways

2015 2016 2017

2015 2016 2017

2015 2016 2017



pathogens developed



MERS-Cov developed


identify & evaluate


develop roadmaps







Review of

prioritisation

methodology

Generic pathogen


methodology

set up

Outlining

appropriate

regulatory &

ethical

pathways

Developing R&D

roadmaps to

accelerate

evaluation of Dxs,

therapeutics &

vaccines


Assessing epidemic

threat & defining

priority pathogens



of epidemics




Regulatory pathways

• Promoting regulatory convergence is

recognized as a key enabler in the R&D Blueprint.

• WHO aims to assist efforts to accelerate research and development by

• outlining appropriate regulatory & ethical pathways, and

• by anticipating evidence needs to inform regulatory review


EUAL listing of Zika IVDs

Overall the submitted technical documentation has been poor, necessitating supplementary laboratory evaluation by WHO. Availability of laboratories to perform the evaluations has

however been a constraint and efforts are ongoing to address the challenges.

As of January 18 2017, 15 applications submitted for ZIKA IVD EUAL remain under evaluation.


Validation and distribution of reference standards for Zika

The international collaborative study to validate the reference standard showed it was suitable for use to calibrate viral load assays in both blood and urine.


Regulatory issues Identification and responding to regulatory gaps

Gaps identified

• NRAs remain unprepared to face a public health emergency

• Lack of NRA capacity in large parts of the developing world.

• Limited capacity and experience in communicating with stakeholders, particularly the media and public.

• Missed opportunity for product developers to engage regulators early and often in the process

• Problems with access to data and samples

• A poorly regulated environment -unscrupulous to take advantage through fake products or dubious remedies.

International Conference of Drug Regulatory Authorities, Cape Town, December 2016 More than 360 regulators from more than 100 WHO Member States


Planned activities 2017: EUAL • Ad Hoc Committee for the Emergency Use of

Vaccines will be convened and advice on the suitability of Ebola vaccines for emergency use is anticipated in Q2 2017

• Proactive identification of laboratories capable of performing IVD evaluation studies on behalf of WHO for each of the priority pathogens will be completed by Q4 2017

• A consultation on options for preparedness to ensure access to products in future emergency settings, will be convened for vaccines, diagnostics and therapeutics against priority pathogens


Planned activities: reference standards

• Completion of an international collaborative study on reference preparations to evaluate the suitability of a candidate WHO reference standard for Zika antibodies is anticipated in Q3 2017

• Work will start in 2017 in WHO Collaborating Centers to

develop candidate reference standards for other priority pathogens (Ebola reference standards have already been established)


Planned activities: regulatory guidelines

• Completion of WHO guidelines on the regulatory evaluation of Ebola vaccines is anticipated in Q3 2017

• A WHO consultation on regulatory expectations for the evaluation of nucleic acid based vaccines will be convened. This will consider the need to update existing guidance on DNA vaccines (WHO Technical Report Series 941) and expand the guidance to mRNA-based vaccines

• A WHO consultation is planned in Q3 2017 to estimate the impact of emerging infections, including Zika, on the blood supply, to facilitate regulatory decision making


Planned activities: joint reviews

• A joint review of clinical trial applications for lead candidate Zika vaccines is being considered, contingent upon interest from the vaccine developers and requests from countries targeted for the forthcoming multi-country clinical trials

What are the anticipated benefits? A global regulatory resource is available to provide pro-active and convergent, but non-binding, advice concerning candidate products being developed against pathogens with the potential to cause public health emergencies of international concern. Global regulatory capacity to respond to public health emergencies of international concern is increased, and readiness improved. Issues of liability in case of mass vaccination with a product which has not yet been fully evaluated, do not slow down deployment of a needed vaccine.

Developing new norms and standards adapted to the epidemic context

2015 2016 2017

2015 2016 2017

2015 2016 2017


Tools: Methods design discussion, decision tree, annotated

generic protocol

Biobanking platforms

process initiated

Review of general agreement forms & guidelines to support framing of collaborations

MTA capacity building tool



Draft tools

available for

vaccines Steps outlined to

develop tools to inform

discussions on trial

designs

Review of

progress of 4

working parties

Anticipating

evidence needs

to inform

regulatory

review and

policy

development

Developing

guidance & tools

to frame

collaborations

and exchanges

Supporting expansion

of capacity to

implement adequate

study designs

Wider consultation on

tools for vaccines starts

Initiate work for

therapeutics

Consultation on ownership,

benefit sharing & IP

Consultation biobanking +

decision tree data sharing

WHO Statement Data sharing

Develop global norms for sharing data & results during public health emergencies

Consultation on

data sharing

SAGE recommendation on evidence need

for policy making on Ebola vaccines


March 2016 30 leading experts met to discuss the rationale of designing a vaccine efficacy trial during public health emergencies and agreed on a collaborative research preparedness exercise . The group includes experts in public health, vaccine trial methodologists, biostatisticians, infectious pathogen modelers, regulators, ethicists and funders. October 2016 30 leading experts met to develop a plan on vaccines study methods to help decision making related to the clinical evaluation of vaccines for priority pathogens under the Blueprint.

Supporting expansion of capacity to implement adequate study designs


Working groups are developing :

(i) a comprehensive methodological discussion paper on vaccine study designs;

(ii) a decision tree to guide methodology experts during the

design of a vaccine trial and promote discussion around key methodological choices;

(iii) a trial simulator using realistic outbreak scenarios to

assess trials feasibility and;

(iv) generic annotated protocols for various study

designs.



A decision tree to guide methodology experts during the design of a vaccine trial Target Population Endpoint

Randomization Comparator


March 2017 CREDO training workshop: to present scope of work. May 2017 Work is underway with four expert groups. The progress will be presented and discussed. The tools are are expected in the third quarter of 2017. Zika study designs workshops 1st Quarter 2017 A future phase of this work will focus on efficacy trial protocols for therapeutics.



Anticipating evidence needs to inform regulatory review and policy development

SAGE Working Group on Ebola vaccines and vaccination http://www.who.int/wer/2015/wer9050.pdf


March 2017 SAGE Working Group on Ebola Vaccines To review updated evidence on immunogenicity, efficacy, effectiveness and safety of candidate Ebola vaccines and, on the observed and projected impact of different vaccination strategies using compassionate use data and from mathematical models. April 2017 SAGE session for DECISION on Ebola Vaccines Previous SAGE recommendations http://www.who.int/wer/2015/wer9022.pdf?ua=1

Anticipating evidence needs to inform regulatory review and policy development


SAGE Working Group on Ebola Vaccines

To consider the following questions that will be presented for SAGE’s consideration in 2017: o Are there remaining challenges that may prevent access to

Ebola vaccines in future outbreaks, and if yes can SAGE make recommendations on how these might be addressed?

o Is the current evidence sufficient for SAGE to make recommendations regarding the use Ebola vaccines (e.g. rVSV and the Russian vaccine) in case of another Ebola outbreak (pre-licensure and/or post licensure)? • If yes, which recommendations can be proposed? • If not, what key data are missing?

What are the anticipated benefits? Clinical trial designs for testing efficacy of vaccines and therapies against priority pathogens are discussed and agreed before an outbreak. This allows quick implementation in case of need, country ownership and fosters partners’ coordination.

Material Transfer Agreements

Development of a capacity building tool

2015 2016 2017

2015 2016 2017

2015 2016 2017



generic protocol


process initiated





Draft tools

available for




designs

Review of

progress of 4

working parties

Anticipating

evidence needs

to inform

regulatory

review and

policy

development

Developing

guidance & tools

to frame

collaborations

and exchanges


of capacity to

implement adequate

study designs



Initiate work for

therapeutics







Consultation on

data sharing




Consultation on an MTA guidance tool

• Held in collaboration with Institute Pasteur

• Focused on public health emergencies

• Convened diverse stakeholder communities to:

• Lessons from recent PHEICs

• Cross-cutting issues

• Contents of MTAs – inc. ownership, benefit sharing & IP

• Did not attempt to resolve differences of opinion or develop a single model

• Did further efforts to map different approaches & options

16 December 2016. Paris, France


Consolidating diverse discussions

• May 2015 – WHO 1st Consultation on Biobanking

• August 2015 – WHO 2nd Consultation on Biobanking

• September 2015 – WHO consultation on data sharing

• January 2016 – Wellcome Trust meeting on biobanking tools

• April 2016 – WHO policy statement on data sharing

• May 2016 – Wellcome Trust meeting on IP, benefit sharing & public health emergencies

Past meetings


Consolidating diverse discussions

• Chatham House project to build tools to strengthen sharing of routine public health surveillance data

• Duke University mapping of legal texts under the Global Healthcare Innovation Alliances

• OpenMTA developed by the Biobricks Foundation & Open Plant Initiative

• MTAs developed and used in an African context by Uganda National Council for Science &Technology

• MSF efforts to prepare for future health emergencies

Other processes and projects


Overview of an MTA tool

Informal consultation noted tool will need to provide:

• An introductory overview of MTAs

• A guide to overarching principles

• Further detail of what is expected in an MTA

• Guidance on how agreements in different areas of an MTA relate to one another.

• The different possible approaches, and how to go about constructing them

• Case studies.

Scope & contents


Next steps & future work

• Develop a draft MTA tool based on existing material (2017 Q1)

• Expand the stakeholders involved through an online public consultation (2017 Q1)

• Revise draft contents & feed into WHO 3rd Biobanking consultation (2017 Q2)

• Test material with possible users (inc. relevant ministries and end users) (2017 Q2-3 onwards)

• Develop digital tool & make available in public beta test (2017 Q3 onwards)

What are the anticipated benefits? Guidance and tools enable barriers to data and sample sharing to be incrementally addressed, so that timelines are accelerated in future outbreaks. This allows control measures to be better implemented, available interventions to be more effectively deployed, and experimental interventions to be evaluated efficiently.

Developing guidance and tools for collaborations and exchanges

Data and sample sharing

2015 2016 2017

2015 2016 2017

2015 2016 2017



generic protocol


process initiated





Draft tools

available for




designs

Review of

progress of 4

working parties

Anticipating

evidence needs

to inform

regulatory

review and

policy

development

Developing

guidance & tools

to frame

collaborations

and exchanges


of capacity to

implement adequate

study designs



Initiate work for

therapeutics







Consultation on

data sharing



79

Data Sharing: Consensus on the need for change


Research data sharing in outbreaks/PHE

Sep 2015 R&D Blueprint consultation has been taken up and “ownership” is felt by several groups as a consensus statement.

Wellcome Trust has been identified as lead party under Global Coordination Mechanism. WHO works to support Wellcome in this role.

Some progress in articulation of enabling policies:


Research data sharing in outbreaks/PHE

Some progress in articulation of enabling policies: • Operationalising WHO policy statement on data sharing in the

context of PHE through developing data sharing frameworks for different categories of stakeholders with different types of data

• Genetic sequence data: Code of conduct for rapid sharing of pathogen genome sequencing in outbreaks

• Medical Journals: Working with ICMJE on enabling policy for pre-publication information sharing (eg Zika open)

• Multiple audiences (funders, researchers, member states): Guidance on data sharing agreements between 3rd parties

• R&D Funders: Engaging with GLOPID-R network of funders on data sharing policies


Challenges to overcome Developing an effective system of incentives for data sharing

Agreeing norms, principles and developing capacities for 3rd party data sharing platforms

Mainstreaming pre-publication platforms (eg BioRxiv, F1000Research)

Ethical issues – 2 related WHO guidance documents (surveillance, outbreaks)

Legal issues – guidance on data sharing agreements

Capacity development in low income settings


WHO Guidance for managing ethical issues in infectious pathogen outbreaks -

2016

http://apps.who.int/iris/bitstream/10665/250580/1/9789241549837-eng.pdf.

apps.who.int/iris/bitstream/10665/250580/1/9789241549837-eng.pdf











Linking with other key initiatives – Chatham House Public Health Surveillance Data Sharing Initiative


Compliance with registration and reporting of clinical trials

Operationalizing WHO policy based on position statement from 2015

– Universal prospective registration in WHO ICTRP compliant registry

– Public disclosure of summary results within 12 months of study completion (shorter timelines during ongoing emergency!)

Developing WHO action plan/checklist for actions for different stakeholders

Global Clinical Trials activity to go live in WHO R&D Observatory later this month

Looking for resources to provide ongoing tracking of trials reporting to WHO ICTRP database


Conclusion

Multiple areas of incremental but not game-changing progress

Some progress in articulation of enabling policies

Still issues in implementation

Trust will be paramount

What are the anticipated benefits? Guidance and tools enable barriers to data and sample sharing to be incrementally addressed, so that timelines are accelerated in future outbreaks. This allows control measures to be better implemented, available interventions to be more effectively deployed, and experimental interventions to be evaluated efficiently.

R&D response to outbreaks

Streamlined operational R&D response during outbreaks


Response to Zika WHO Incident Management Structure

Partner Coordination

Management & administration

Technical expertise

(Research)

Field operations

& support

Communications

Resource Mob.

Leadership

Health Operations

Information & Planning

Operations Support and

Logistics

Research agenda

3 WHO clusters (OHE; FWC; HIS), and PAHO


Blueprint Zika R&D activities

• Landscape analysis of products

• Diagnostic TPP to detect active infection/prior infection

• Emergency Use Assessment & listing (EUAL) procedure

• Reference reagents

• Vaccine TPP to protect against Congenital Zika Syndrome for use during an emergency

• WHO Vaccine Pipeline Tracker


Blueprint ZIKA R&D meetings

- WHO global consultation of research related to Zika virus infection.

7-9 March 2016; Geneva

- WHO consultation for the EUAL procedure for Diagnostics.

14-15 March 2016; Geneva

- WHO consultation on considerations for regulatory expectations of Zika virus vaccines for use during an emergency.

6-7 June 2016; Geneva

- A common approach to tackling mosquito-borne viruses to pre-empt

epidemics. WHO-Wellcome Trust, 5-7 October 2016; London

- Scientific Consultation on ZIKV vaccine. NIAID-WHO, 10-11 January 2017; Washington


ZIKA: Post emergency plan Emergency Committee 18 November 2016

• Zika virus and associated consequences remain a significant enduring public health challenge requiring intense action but no longer represent a PHEIC as defined under the IHR

• Robust longer-term technical mechanism is now required to manage the global Zika response

Transition plan towards a long-term programme


R&D response mechanisms

WHO Steering Committee HIS/FWC/WHE

Internal WHO coordination and planning

Operational plan Decision tree


Decision tree WHO becomes aware of an epidemic relevant for the R&D Blueprint

Is the Pathogen on the list of priority pathogens?

Unknown or with unusual characteristics

Decision tree for emergency prioritization

No further action

Prioritized pathogen

N Y

What are the outbreak characteristics and MCMs available

No to all

No further action

Yes to any

Inform the steering

committee

Do not know to any

Criteria 1

Criteria 2

….

Criteria n

Y

N


Operational plans

Three outbreak scenarios – Priority pathogens with no MCMs available,

– Priority pathogens with some MCMs available

– Outbreaks caused by an unknown pathogen

Detailed operational plans for: – Staffing and budget needs

– Reallocation of staff

– Additional resource needs

WHO Global (product and non-product) Research Agenda


Blueprint R&D response to an epidemic

WHO Steering Committee HIS/FWC/WHE

Global Coordination Mechanism

Operational plan Decision tree

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